Stimulation of dopaminergic amacrine cells by stroboscopic illumination or fibroblast growth factor (bFGF, FGF-2) injections: possible roles in prevention of form-deprivation myopia in the chick

Brain Res. 1995 Jul 24;686(2):169-81. doi: 10.1016/0006-8993(95)00370-6.

Abstract

Form-deprivation myopia (FDM) in the chick is a popular model for studying the postnatal regulation of ocular growth. Using this model, we have shown previously that dopamine and FGF-2 can counteract the effects of form-deprivation, thereby producing emmetropia. In the present study, we tested the hypothesis that the emmetropizing effects of flickering light and intraocular injections of FGF-2 in the chick are mediated by the activity of dopaminergic retinal amacrine cells. We have assessed the rate of dopamine synthesis in the retina by measuring the accumulation of 3,4-dihydroxyphenylalanine (DOPA). We found that form-deprivation reduces the rate of dopamine synthesis in the light-adapted retina, and that the normal rate of dopamine synthesis in the light can be restored by stroboscopic illumination at frequencies around 10 Hz. By labeling cells immunocytochemically we have shown that the synthesis of c-fos, a putative transcriptional regulator of the tyrosine hydroxylase gene, is induced in dopaminergic amacrine cells by stroboscopic illumination at around 10 Hz. These observations are consistent with a critical role for dopaminergic amacrine cells in the regulation of ocular growth by intermittent illumination. We have found also that intraocular injections of FGF-2 cause emmetropization without altering levels of expression of c-fos, amounts of tyrosine hydroxylase, or rates of dopamine synthesis with respect to vehicle-injected controls. We conclude that FGF acts either in parallel to or downstream from the dopaminergic amacrine cells, rather than through them. We observed that intravitreal injection per se induces high levels of c-fos expression in both form-deprived and non-deprived retinas, and causes partial emmetropization in form-deprived eyes, while inhibiting dopamine synthesis in non-deprived retinas. It is likely, therefore, that injection stimulates the production and/or release of unknown factors whose diverse effects on ocular growth and dopamine metabolism are mediated by complex pathways. Taken together, our results are consistent with the view that the retinal circuitry that controls postnatal ocular growth in the chick involves multiple messengers and pathways.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Chickens
  • Dopamine / physiology*
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factors / pharmacology*
  • Immunohistochemistry
  • Male
  • Myopia / etiology
  • Myopia / prevention & control*
  • Photic Stimulation / methods
  • Proto-Oncogene Proteins c-fos / metabolism
  • Retina / cytology
  • Retina / physiology*
  • Sensory Deprivation / physiology*
  • Tyrosine 3-Monooxygenase / metabolism
  • Vision, Ocular*

Substances

  • Proto-Oncogene Proteins c-fos
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factors
  • Tyrosine 3-Monooxygenase
  • Dopamine